Circular dichroism has been shown to offer a powerful probe of the 3-dimensional fine structure of the antibody combining site, capable of detecting small differences between antibodies of closely similar specificity. The amino-terminal halves of the light chains display type-specific amino acid sequences and appear to be encoded by members of a set of type-specific variables genes which associate only with a single carboxy-terminal light chain cistron. In contrast, the amino-terminal sequences of heavy chains appear to be specified by members of a set of heavy chain variable genes which may be associated with any of the several class-specific carboxyl-terminal heavy chain cistrons. The expanded two-gene hypothesis for heavy chain variability offers a conservative mechanism to generate multiple molecular forms of antibody of identical specificity. The present investigations propose to test this hypothesis by examining distinct molecular forms of antibody of similar specificity, synthesized in the same animal. Antigens have been developed (e.g., Dnp-gramicidin-S) which are capable of stimulating and maintaining the production of homogeneous anti-hapten antibody. The fine structure of the combining sites of homogeneous antibodies and distinct molecular forms of antibody of similar specificity, as well as of mouse MOPC-315 and -460 IgA myeloma protein, are being compared in detail by analysis of the induced circular dichroism generated upon binding a range of haptens.